A higher anti-Müllerian hormone level is associated with an increased chance of pregnancy in patients undergoing controlled ovarian stimulation and intrauterine insemination.

Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.

Developing comprehensive and Brief ICF core sets for morbid obesity for disability assessment in Taiwan: a preliminary study.

BACKGROUND: The International Classification of Functioning, Disability, and Health (ICF) provides a framework for measuring functioning and disability based on a biopsychosocial model. AIM: The aim of this study was to develop comprehensive and brief ICF core sets for morbid obesity for disability assessment in Taiwan. DESIGN: Observational SETTING: Other POPULATION: Twenty-nine multidisciplinary experts of ICF METHODS: The questionnaire contained 112 obesity-relevant and second-level ICF categories. Using a 5-point Likert scale, the participants rated the significance of the effects of each category on the heath status of people with obesity. Correlation between an individual's score and the average score of the group indicated consensus. The categories were selected for the comprehensive core set for obesity if more than 50% of the experts rated them as "important" in the third round of the Delphi exercise, and for the brief core set if more than 80% of the experts rated them "very important." RESULTS: Twenty-nine experts participated in the study. These included 18 physicians, 4 dieticians, 3 physical therapists, 2 nurses, and 2 ICF experts. The comprehensive core set for morbid obesity contained 61 categories. Of these, 26 categories were from the component body function, 8 were from body structure, 18 were from activities and participation, and 9 were from environmental factors. The brief core set for obesity disability contained 29 categories. Of these, 19 categories were from the component body function, 3 were from body structure, 6 were from activities and participation, and one was from environmental factors. The comprehensive and brief ICF core sets provide comprehensive information on the health effects of morbid obesity and concise information for clinical practice. CONCLUSION: Comprehensive and brief core sets were created after three rounds of Delphi technique. Further validation study of these core sets by applying to patients with morbid obesity is needed. CLINICAL REHABILITAITON IMPACT: The comprehensive ICF core set for morbid obesity provides comprehensive information on the health effects of morbid obesity; the brief core set can provide concise information for clinical practice.

Risk of colorectal cancer in women with pelvic inflammatory disease: a matched cohort study.

OBJECTIVE: Inflammation is an important risk factor for the development of colorectal cancer (CRC). Pelvic inflammatory disease (PID) comprises a spectrum of upper genital tract infections and inflammatory diseases. We aimed to evaluate the association between CRC and PID. DESIGN: Matched cohort study using the National Health Insurance Research Database. SETTING: Women with PID in Taiwan. POPULATION AND SAMPLE: From the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan, we obtained data on women from 13 to 45 years of age who were diagnosed with PID. The women with PID were matched 1:4 to selected members of the population without PID based on age and year of first entry into the LHID2005. METHODS: A Cox proportional hazards model was used to evaluate the hazard ratio for CRC during the 5-year follow-up period, after adjusting for sociodemographic characteristics and selected comorbid medical disorders. MAIN OUTCOME MEASURES: Colorectal cancer. RESULTS: Of the 19,029 women with PID, 30 were diagnosed with CRC during the 78,965 person-year follow-up period. Of the 76,116 control women, 66 were diagnosed with CRC. The CRC hazard ratio during the 5-year follow-up period was 2.00 (95% CI 1.30-3.08) for women with PID relative to control women. Similarly, after adjusting for age, Charlson comorbidity index score, urbanisation level and monthly income, the adjusted CRC hazard ratio was 1.71 (95% CI 1.10-2.65) for the women with PID relative to the women in the comparison cohort. CONCLUSIONS: Here we show a weak association between PID and CRC. Additional studies are needed to further evaluate this association and examine plausible mechanisms, including the influence of specific microorganisms.

The dipeptidyl peptidase-4 inhibitor-sitagliptin modulates calcium dysregulation, inflammation, and PPARs in hypertensive cardiomyocytes.

BACKGROUND: Hypertension induces cardiac dysfunction, calcium (Ca(2+)) dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an antidiabetic agent with anti-inflammation and anti-hypertension potential, may regulate peroxisome proliferator-activated receptors (PPARs)-α, -γ, and -δ and Ca(2+) homeostasis. OBJECTIVE: The purpose of this study was to investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca(2+) handling proteins in hypertensive hearts. METHODS: A Western blot analysis was used to evaluate protein expressions of myocardial PPAR isoforms, tumor necrosis factor (TNF)-α, interleukin (IL)-6, sarcoplasmic reticulum ATPase (SERCA2a), Na(+)-Ca(2+) exchanger (NCX), ryanodine receptor (RyR), voltage-dependent Ca(2+) (CaV1.2), slow-voltage potassium currents (Kvs), angiotensin II type 1 receptor (AT1R), and receptor of advanced glycated end-products (RAGE) from Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with sitagliptin (10mg/kg for 4weeks). Conventional microelectrodes were used to record action potentials (APs) in the ventricular myocytes from each group. RESULTS: Compared to the control group, SHR had lower cardiac PPAR-α and PPAR-δ protein expressions, but had greater cardiac PPAR-γ levels, and TNF-α, IL-6, RAGE, and AT1R protein expressions, which were ameliorated in the sitagliptin-treated SHR. SHR had prolonged QT interval and AP duration with less SERCA2a and RyR, and greater CaV1.2 expressions, which were also attenuated in sitagliptin-treated SHR. CONCLUSIONS: Sitagliptin significantly changed the cardiac electrophysiological characteristics and Ca(2+) regulation, which may have been caused by its effects on cardiac PPARs, proinflammatory cytokines, and AT1R.

Kruger strict morphology and post-thaw progressive motility in cryopreserved human spermatozoa.

The purpose of this prospective study was to evaluate Kruger strict morphology and conventional semen analysis in predicting cryosurvival and the progressive motility recovery rate of frozen spermatozoa. Our study included 56 semen samples with >10 million spermatozoa per ejaculate. The main outcome measures were conventional semen analysis, strict morphology analysis by the Kruger method, cryosurvival rate and post-thaw sperm motility. A significant reduction in sperm motility after cryopreservation was demonstrated. The freeze-thawing process caused a 66% reduction in rapid progressive motile spermatozoa, a 45% reduction in slow progressive motile spermatozoa and a 2% reduction in nonprogressive motile spermatozoa. The cryosurvival and progressive motility recovery rates were not correlated with parameters of conventional semen analysis, such as sperm concentration, motility, WHO morphology and total motile count, but the progressive motility recovery rate was significantly correlated with the percentage of spermatozoa exhibiting Kruger normal morphology (P = 0.028). The recovery rate of rapidly progressive motility was profoundly decreased compared with slow progressive motility following the frozen-thaw procedure of semen. Kruger strict morphology assessment was a better predictor of the progressive motility recovery rate following the freezing-thaw procedure than parameters of conventional semen analysis.

Is the timing of implantation affected by zona pellucida micromanipulation?

PURPOSE: Our purpose was to examine the timing of implantation and early embryo development following uterine transfer of oocytes/embryos previously subjected to zona pellucida micromanipulation. METHODS: A total of 68 singleton pregnancies resulting from IVF and embryo transfer with/without micromanipulation. Patients were divided into four groups according to the type of micromanipulation technique: assisted hatching, embryo biopsy, intracytoplasmic sperm injection, and no micromanipulation (control group). Serial serum beta-hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG10) to estimate detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG, an indirect sign of embryo development. RESULTS: There were no significant differences among groups with respect to hCG10, the slopes or intercepts of the regression lines. CONCLUSIONS: Various oocyte/embryo microsurgical procedures used in ART involving zona pellucida manipulation do not appear to affect the timing of implantation or early embryo development.

Embryo implantation in in vitro fertilization and intracytoplasmic sperm injection: impact of cleavage status, morphology grade, and number of embryos transferred.

OBJECTIVE: The aims of this study were to compare preimplantation embryo quality in intracytoplasmic sperm injection (ICSI) with standard IVF and to examine the impact of age and number and quality of embryos transferred on implantation and pregnancy. DESIGN: Retrospective, controlled clinical study. SETTING: Academic tertiary center. PATIENT(S): We examined 211 consecutive couples undergoing ICSI who were matched with 211 couples undergoing IVF therapy during the same time frame. INTERVENTION(S): In vitro embryo culture. MAIN OUTCOME MEASURE(S): Day 3 embryo quality as judged by the number of blastomeres and morphology scoring. RESULT(S): Patients undergoing ICSI had a significantly reduced number of embryos with good morphology and cleavage compared with IVF cases. Nevertheless, pregnancy and abortion rates were similar when adjusted by age and number of embryos transferred. Average cleavage status and age were significant predictors of implantation. Women of advanced age had significantly lower embryo cleavage and implantation rates. CONCLUSION(S): [1] The cleaving status of day 3 embryos is a valuable, although limited, indicator of implantation outcome. [2] In vitro fertilization-derived embryos had better cleavage rates and morphology scores than ICSI-derived embryos; however, the implantation potential was similar for both groups. [3] The age-related decline in implantation rate was associated with impaired embryo growth rates.

Perifollicular blood flow Doppler indices, but not follicular pO2, pCO2, or pH, predict oocyte developmental competence in in vitro fertilization.

OBJECTIVE: To assess the relationships among perifollicular blood flow; follicular fluid pO2, pCO2, and pH; oocyte developmental capacity; preimplantation embryo quality. DESIGN: Prospective study. SETTING: Academic, tertiary care institution. PATIENT(S): Unselected, gonadotropin-stimulated IVF cycles. INTERVENTION(S): Color, pulsed Doppler analysis of perifollicular blood flow, and follicular pO2, pCO2, and pH determinations of randomly designated, mapped ovarian follicles. MAIN OUTCOME MEASURE(S): Fertilization and day 3 embryo cleavage and morphology. RESULT(S): Perifollicular vascularity indices were significantly and negatively correlated with day 3 embryo cleavage. Pulsatility index and S-D ratio also were significantly and negatively correlated with follicular pO2. The same correlation was found between resistance index and the fertilization rate of preovulatory oocytes. No relationship existed between follicular metabolic analysis and fertilization or embryo quality. The resistance index had a sensitivity of 0.57 and a specificity of 0.71 for the prediction of advanced embryo cleavage status. CONCLUSION(S): Results confirm and extend previous reports demonstrating that color, pulsed Doppler ultrasound analysis of individual preovulatory follicles during IVF therapy may provide an indirect index of the developmental competence of the corresponding oocyte. Although these methods may provide means to select embryos for transfer with the highest implantation potential, the moderate predictive power showed so far may limit their clinical applicability.

Expression of gonadotropin-releasing hormone (GnRH) gene in human uterine endometrial tissue.

Many peripheral reproductive tissues have been found to contain gonadotrophin-releasing hormone (GnRH) and express the GnRH gene at low levels, presumably because the hormone functions in a paracrine/autocrine fashion. This study was designed to investigate and characterize GnRH gene expression in human endometrial tissue at different stages of the endometrial cycle. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis together with Southern blot assay demonstrated that human endometrial tissue expresses the proGnRH gene. RNA samples from endometrial tissue were analysed with two pairs of oligonucleotide primers. Both gave a doublet 870 bases apart at the expected sizes, indicating that both the upstream and downstream transcriptional start sites of the GnRH gene are used in endometrial tissue and that transcripts with and without intron 1 were produced. Our data also demonstrated that utilization of the two promoters varies with the stage of the endometrial cycle. The largest difference came from the mRNA transcribed from the downstream promoter and without intron 1. This mRNA was expressed at a very low level during the proliferative phase and dramatically increased almost 10-fold (P < 0.01) during the early secretory phase, and subsequently decreased 5-fold during the late secretory stage. The presence of GnRH mRNA in the endometrium, as well as the differential expression of the GnRH gene during the early secretory phase provides physiological evidence that human GnRH may play a paracrine/autocrine function in the human uterus.

Analysis of implantation in assisted reproduction through the use of serial human chorionic gonadotropin measurements.

PURPOSE: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels. METHODS: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol [gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG10), which was used as an estimate of detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG. RESULTS: There were no significant differences in the days of hCG in maternal serum to reach 10 mIU/ml (implantation) or in the slopes of the regression lines for all five studied groups. CONCLUSIONS: The appearance of hCG in maternal serum was used to assess the time of clinically detectable implantation. Furthermore, because hCG production is a marker of trophoblastic activity, its serum doubling time was used as an indicator of embryo quality. Results showed that in various ART protocols with and without GnRHa, there were no significant differences in implantation time or embryo quality. Embryo development in early pregnancy follows a preprogrammed-timing schedule and depends mainly on the embryonic age of the healthy, successfully implanted conceptus.

Glucocorticoids modulate human gonadotrophin releasing hormone upstream promoter activity in transfected human placental cells (JEG-3).

A human gonadotrophin releasing hormone (GnRH) upstream promoter/luciferase reporter gene construct (H2 construct) was generated by inserting a 1.7 kb XbaI/AflII fragment containing the human GnRH upstream promoter region only into a promoter-less luciferase reporter vector. When JEG-3 cells were transiently transfected with this construct and treated with cortisol or its synthetic analogue dexamethasone, a stimulatory effect on the upstream promoter activity was observed. This stimulation was dependent on the cotransfection of a glucocorticoid receptor (GR) cDNA expression vector due to the low level of GR in JEG-3 cells and could be completely abolished by RU486, a glucocorticoid antagonist. Moreover, the cortisol actions could be modulated to a different extent by oestradiol. Thus, since the human placenta contains GRs and the increase in cortisol metabolism near term is regulated by oestrogen, the current findings suggest that cortisol may be physiologically involved in the regulation of GnRH gene expression in the human placenta.